
Contributions
Abstract: P1740
Type: Poster Sessions
Abstract Category: N/A
Background: Serum neurofilament light chain (sNfL) is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (RRMS). However, data supporting the potential use of sNfL to measure disease progression or response to therapy in secondary progressive multiple sclerosis (SPMS) are comparatively scant.
Objectives: To report associations between sNfL and disease activity, disability progression, and response to natalizumab in SPMS patients enrolled in the ASCEND study.
Methods: sNfL levels were measured at baseline, week 48, and week 96 in 748 patients (randomized to natalizumab [n=379] or placebo [n= 365]) from the phase 3 ASCEND study of natalizumab in SPMS. sNfL levels were assessed using a Single Molecule Array (SIMOA) assay. Statistical analyses included Spearman correlation, mixed model for repeated measure, and ANCOVA.
Results: Baseline sNfL levels were significantly associated with baseline age (p< 0.05), number of Gd+ lesions (p< 0.0001), T2 lesion volume (p< 0.0001), Timed 25-Foot Walk time(T25FW, p< 0.0001), and 9-Hole Peg Test time (9HPT, p< 0.0001). Baseline sNfL levels were also associated with brain atrophy over 96 weeks (p< 0.0001). At week 96, sNfL levels were significantly higher in patients with progression compared to those without progression during the study, as defined using EDSS (p< 0.01), T25FW (p< 0.05), or 9HPT (p< 0.01 for both week 48 and week 96). Finally, sNfL levels at week 48 and week 96 were significantly lower in natalizumab-treated patients compared to those on placebo [ratio 0.84, 95% CI (0.79, 0.89), p< 0.001 and ratio 0.80, 95% CI (0.7, 0.85), p< 0.001, respectively]. Statistically significant differences in sNfL levels between natalizumab and placebo groups were observed in patients with and without enhancing lesions at baseline, relapses in the two years prior to the study enrollment, and inflammatory activity during the study.
Conclusions: Similar to previous observations in patients with RRMS, baseline sNfL levels of SPMS patients in the ASCEND study were associated with baseline disease activity measures and future brain atrophy rates. Natalizumab reduced sNfL levels compared to placebo in SPMS patients with and without acute inflammatory activity. Our findings suggest that sNfL might not only reflect inflammation driven neuro-axonal damage but also non-inflammatory neurodegeneration in MS patients. Further studies are needed to corroborate our observations.
Disclosure: DLA equity interest in NeuroRx during the study and consulting activities with Biogen, Celgene, Genentech, Genzyme, Hoffman-La Roche, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, grants from Biogen and Novartis.
RK: support from UK National Institute of Health Research UCL/H Biomedical Research Centre and personal compensation for consultancies, lectures, participation in advisory boards, and/or support for travel to medical meetings from Actelion, Biogen, Genzyme, Novartis, Roche, Teva.
MDG: personal compensation from Aclimed, Genzyme, and Sarepta for consulting services and from Acorda Therapeutics, Biogen, and Novartis Pharmaceuticals for travel reimbursement. Research support from Biogen, Novartis Pharmaceuticals, and NINDS.
MSF: honoraria or consulting fees from Bayer HealthCare, Biogen, Chugai, EMD Canada, Hoffmann-La Roche, Merck Serono, Novartis, Sanofi Genzyme, Teva Canada Innovation; company advisory boards/boards of directors for Actelion, Bayer HealthCare, Biogen, Hoffmann-La Roche, Merck Serono, Novartis, Opexa, Sanofi Genzyme; participation in a company-sponsored speakers' bureau for Genzyme.
HPH: personal compensation for consulting services and/or speaking at scientific symposia from Biogen, GeNeuro, Genzyme, Merck Serono, Novartis, Octapharma, Opexa, Roche, Teva.
DJ: research funding from Biogen, Genentech; personal compensation for speaking or consulting services from Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Novartis, Questcor, Serono, Teva.
AM: research funding from Acorda, Biogen, Genentech, Genzyme, Novartis, Questcor, Roche, Sanofi; personal compensation for consulting services from Accordant Health Services, Acorda, Alkermes, Biogen, EMD Serono, Genentech, GlaxoSmithKline, Novartis, Roche, Sanofi Genzyme, Teva.
FS: compensation for service on scientific advisory boards, on steering committees of clinical trials, and as a consultant for and/or received support for congress participation, speaker honoraria, or research support for his laboratory from Biogen, EMD Serono, Genzyme, Merck, Novartis, Roche, Sanofi, Teva.
KRE: Consulting fees (Biogen, Genzyme, EMD Serono); research support (Biogen, Eli Lilly, Genentech, Sanofi, and Hoffmann-La Roche, Novartis).
TP, CS, IC, DS, BZ, SS, DM, EF, P-RH, NC, BK, RR, RZ, ME are employees of and hold stock and/or stock options in Biogen
Abstract: P1740
Type: Poster Sessions
Abstract Category: N/A
Background: Serum neurofilament light chain (sNfL) is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (RRMS). However, data supporting the potential use of sNfL to measure disease progression or response to therapy in secondary progressive multiple sclerosis (SPMS) are comparatively scant.
Objectives: To report associations between sNfL and disease activity, disability progression, and response to natalizumab in SPMS patients enrolled in the ASCEND study.
Methods: sNfL levels were measured at baseline, week 48, and week 96 in 748 patients (randomized to natalizumab [n=379] or placebo [n= 365]) from the phase 3 ASCEND study of natalizumab in SPMS. sNfL levels were assessed using a Single Molecule Array (SIMOA) assay. Statistical analyses included Spearman correlation, mixed model for repeated measure, and ANCOVA.
Results: Baseline sNfL levels were significantly associated with baseline age (p< 0.05), number of Gd+ lesions (p< 0.0001), T2 lesion volume (p< 0.0001), Timed 25-Foot Walk time(T25FW, p< 0.0001), and 9-Hole Peg Test time (9HPT, p< 0.0001). Baseline sNfL levels were also associated with brain atrophy over 96 weeks (p< 0.0001). At week 96, sNfL levels were significantly higher in patients with progression compared to those without progression during the study, as defined using EDSS (p< 0.01), T25FW (p< 0.05), or 9HPT (p< 0.01 for both week 48 and week 96). Finally, sNfL levels at week 48 and week 96 were significantly lower in natalizumab-treated patients compared to those on placebo [ratio 0.84, 95% CI (0.79, 0.89), p< 0.001 and ratio 0.80, 95% CI (0.7, 0.85), p< 0.001, respectively]. Statistically significant differences in sNfL levels between natalizumab and placebo groups were observed in patients with and without enhancing lesions at baseline, relapses in the two years prior to the study enrollment, and inflammatory activity during the study.
Conclusions: Similar to previous observations in patients with RRMS, baseline sNfL levels of SPMS patients in the ASCEND study were associated with baseline disease activity measures and future brain atrophy rates. Natalizumab reduced sNfL levels compared to placebo in SPMS patients with and without acute inflammatory activity. Our findings suggest that sNfL might not only reflect inflammation driven neuro-axonal damage but also non-inflammatory neurodegeneration in MS patients. Further studies are needed to corroborate our observations.
Disclosure: DLA equity interest in NeuroRx during the study and consulting activities with Biogen, Celgene, Genentech, Genzyme, Hoffman-La Roche, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, grants from Biogen and Novartis.
RK: support from UK National Institute of Health Research UCL/H Biomedical Research Centre and personal compensation for consultancies, lectures, participation in advisory boards, and/or support for travel to medical meetings from Actelion, Biogen, Genzyme, Novartis, Roche, Teva.
MDG: personal compensation from Aclimed, Genzyme, and Sarepta for consulting services and from Acorda Therapeutics, Biogen, and Novartis Pharmaceuticals for travel reimbursement. Research support from Biogen, Novartis Pharmaceuticals, and NINDS.
MSF: honoraria or consulting fees from Bayer HealthCare, Biogen, Chugai, EMD Canada, Hoffmann-La Roche, Merck Serono, Novartis, Sanofi Genzyme, Teva Canada Innovation; company advisory boards/boards of directors for Actelion, Bayer HealthCare, Biogen, Hoffmann-La Roche, Merck Serono, Novartis, Opexa, Sanofi Genzyme; participation in a company-sponsored speakers' bureau for Genzyme.
HPH: personal compensation for consulting services and/or speaking at scientific symposia from Biogen, GeNeuro, Genzyme, Merck Serono, Novartis, Octapharma, Opexa, Roche, Teva.
DJ: research funding from Biogen, Genentech; personal compensation for speaking or consulting services from Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Novartis, Questcor, Serono, Teva.
AM: research funding from Acorda, Biogen, Genentech, Genzyme, Novartis, Questcor, Roche, Sanofi; personal compensation for consulting services from Accordant Health Services, Acorda, Alkermes, Biogen, EMD Serono, Genentech, GlaxoSmithKline, Novartis, Roche, Sanofi Genzyme, Teva.
FS: compensation for service on scientific advisory boards, on steering committees of clinical trials, and as a consultant for and/or received support for congress participation, speaker honoraria, or research support for his laboratory from Biogen, EMD Serono, Genzyme, Merck, Novartis, Roche, Sanofi, Teva.
KRE: Consulting fees (Biogen, Genzyme, EMD Serono); research support (Biogen, Eli Lilly, Genentech, Sanofi, and Hoffmann-La Roche, Novartis).
TP, CS, IC, DS, BZ, SS, DM, EF, P-RH, NC, BK, RR, RZ, ME are employees of and hold stock and/or stock options in Biogen